Thanks also to Marian Showell (Trials Search Coordinator) for designing and running multiple searches for the 2009 and 2015 updates. The results favoured indomethacin, but the statistical significance of this finding was not reported (see Table 14). Litt IF, We planned to subgroup studies by the type of NSAID used (nonselective or COX2specific inhibitors) if there were sufficient studies in each group that reported the same outcome (for example, three or more studies in each group). 28 trial.ti. 10 (non$steroidal adj5 anti$inflammator$).tw. 5 pelvic pain.tw. daily dose 1250 mg), List of symptoms and number of women experiencing them before and after treatment, No denominator reported for adverse effect data, Inclusion: women with primary dysmenorrhoea, complete physical and pelvic exams, Naproxen sodium (550 mg initially, then 275 mg every 6 hours as needed, max. 3 withdrew, 2 not eligible, 1 withdrawn by physician, Mefenamic acid, dextropropoxyphene and paracetamol, flufenamic acid, 56 women, crossover trial, Pyrasanone, placebo, 20 women, crossover trial, Nimesulide, piroxicam, 26 women, parallel trial, Compares valdecoxib and piroxicam. For 24 hour advice, contact Victorian Poisons Information Centre 13 11 26 Background Martin VT, [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword] (4293) When NSAIDs were compared with each other, most studies found no evidence of a difference between them. We retrieved 18 articles for further assessment regarding their eligibility, 10 from databases (for which we obtained the full text) and eight from trial registers. Seven studies reported data suitable for metaanalysis for this outcome. Daftary SN, Comparison 1 NSAIDs vs placebo, Outcome 9 All adverse effects. The review found that NSAIDs appear to be very effective in relieving period pain. We took a P value of less than 0.1 for the Chi2 test to indicate significant heterogeneity and if this was detected, we used the I2 statistic to estimate the percentage of the variability in effect estimates due to heterogeneity rather than sampling error. 15 (rofecoxib$ or valdecoxib$).tw. risk of bias), consistency of effect, imprecision, indirectness and publication bias). Absence from work/school: NSAIDs versus placebo (per cycle data). The antiinflammatory and painrelieving effects of NSAIDs are thought to be mainly due to inhibition of COX2 enzymes, whereas the side effects (commonly gastrointestinal) appear to be related to the inhibition of COX1 enzymes. Mannix LK, We deemed the risk of bias unclear if the study was described as randomised but the sequence generation method was not described. Copyright 2023 American Academy of Family Physicians. Only two of the included studies utilised COX2specific inhibitors (etoricoxib and celecoxib). (23270) Vail A. Metaanalyses involving crossover trials: methodological issues. 14 exp Cyclooxygenase 2/ (29849) As a result their findings may have been underweighted in analysis, resulting in wider confidence intervals than would otherwise be the case. Farquhar C. Behavioural interventions for dysmenorrhoea. Worthington HV, NA. Cortes RJR, The addition of NSAIDs to other medical treatments has not been well studied. Zuuren EJ. Jamil MA, With respect to risk of bias, most studies considered for this review were of poor calibre. No evidence of a difference was found between naproxen and individual NSAIDs for this outcome, nor was there any evidence of a difference between naproxen versus the other NSAIDs when we pooled the data. Our findings are in accordance with a systematic review of NSAIDs and hormonal contraceptives for dysmenorrhoea published in 2010 (Zahradnik 2010), which was based on a search of a single database (PubMed). Two additional studies reported only percycle data. The dosages of mefenamic acid in these studies were higher than the typical recommended dosing in the United States, which is a single dose of 500 mg, followed by 250 mg four times daily for up to three days. We deemed the risk of bias unclear if the study was described as blinded but no further details were reported. 13 nsaid$.tw. Bethesda, MD 20894, Web Policies Doubova SV, An increase in the odds of a particular outcome, which may be beneficial (for example, pain relief) or detrimental (for example, an adverse effect), is displayed graphically in the metaanalyses to the right of the centreline and a decrease in the odds of an outcome to the left of the centreline. The quality of the included studies is summarised in Figure 4. The review includes 80 RCTs, 24 of parallel design and 56 of crossover design. Nasiri Amiri F, We deemed the risk of bias unclear if the study was described as randomised but the method used for allocation concealment was not described. Shoffitt T, There were 18 studies comparing NSAIDs headtohead from which data suitable for metaanalysis could be extracted, only two of which compared the same two NSAIDs (Daniels 2009a; Daniels 2009b). Altman DG, Scott JN, The studies analysed a total of 2602 women, 2006 women in crossover trials and 596 women in parallel trials. Fariborz M, 'Risk of bias' summary: review authors' judgements about each methodological quality item for each included study. 3 days, dose could be reduced if needed), Proportion with decrease in pain, weakness/dizziness/nausea and diarrhoea, Groups compared at baseline and trial also reported mean differences in pain from entry score for end of first phase. Kotey P, The results of this review, although based on small and mostly underpowered studies without data amenable to pooling, are consistent with the recommendations from the National Institute for Health and Care Excellence, suggesting that the levonorgestrel-releasing intrauterine system be the initial treatment for heavy menstrual bleeding. Bentley A, Groth K. Nonsteroidal antiinflammatory drugs and hormonal contraceptives for pain relief from dysmenorrhea: a review, Efficacy of minor analgesics in primary dysmenorrhoea: a systematic review, British Journal of Obstetrics and Gynaecology. 8 exp antiinflammatory agents, nonsteroidal/ or exp cyclooxygenase inhibitors/ (455220) However, there was only one study for each comparison. Comparative study of ibuprofen and mefenamic acid, Mefenamic acid (Ponstel) for treating primary spasmodic dysmenorrhea, Alterations in intrauterine pressure, menstrual fluid prostaglandin F levels, and pain in dysmenorrheic women treated with nimesulide. Gyrffy Z, Comparison 7 Naproxen vs NSAIDs, Outcome 6 All adverse effects. Artigas R, Simonin G, in heavy menstrual bleeding (menorrhagia) Based on 56 reports of heavy menstrual bleeding (menorrhagia) community members. Emery MG, A doubleblind, crossover study, A general practice study of naproxen sodium and a dextropropoxypheneparacetamol combination in primary dysmenorrhoea, Comparison between naproxen tablets and suppositories in primary dysmenorrhea, Comparison between fluproquazone and indomethacin in treatment of primary dysmenorrhoea, Comparative efficacy, safety and cost effectiveness of lornoxicam with ibuprofen in patient with primary dysmenorrhoea: a randomized, doubleblind, activecontrolled study, http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=3443, Prevalence and impact of dysmenorrhea on Hispanic female adolescents, Archives of Pediatrics and Adolescent Medicine, Nonsteroidal antiinflammatory drugs differences and similarities, http://www.consortstatement.org/consortstatement/, Primary dysmenorrhea: advances in pathogenesis and management. Coreysart 7 years ago. The available evidence suggests that if 10% of women taking placebo experience side effects, between 11% and 14% of women taking NSAIDs will do so. Lundstrom V, Comparison 1 NSAIDs vs placebo, Outcome 3 Pain relief continuous data: total pain relief score difference. For continuous data (e.g. Ertungealp E, (3592) Marti ML, Celecoxib was less effective for pain relief than naproxen and there was no evidence of any difference between etoricoxib and naproxen. Mechanism of action. See Figure 1. Prevalence and correlates of three types of pelvic pain in a nationally representative sample of Australian women, Herbal and dietary therapies for primary and secondary dysmenorrhoea. Mefenamic acid, an anthranilic acid derivative, is a member of the fenamate group of nonsteroidal anti-inflammatory drugs (NSAIDs). Scott JR. Dysmenorrhea: treatment with an antiprostaglandin, Treatment of primary dysmenorrhea with prostaglandin synthetase inhibitors a promising therapeutic alternative, Endogenous prostaglandins in dysmenorrhea and the effect of prostaglandin synthetase inhibitors (PGSI) on uterine contractility, A comparison of flurbiprofen and paracetamol in the treatment of primary dysmenorrhoea, Menstrual blood loss in dysmenorrhoea: effects of proquazone and indomethacin. (170486) 1Very poor reporting of study methods by over 75% of studies; high risk of attrition bias in several studies; over 60% of studies commercially sponsored. Minic M, Burt RA, 26 drug comparison/ (81319) Lacoste C. Doubleblind placebocontrolled study of the efficacy of niflumic acid (750 mg/day in three divided doses) in dysmenorrhea, Revue Francaise de Gynecologie et d'Obstetrique. We considered blinding adequate if any of the following were described: We deemed the risk of bias low if one of these methods was described. Hernandez SF, (198) Crossover trials are suitable for evaluating interventions with a temporary effect in the treatment of stable, chronic conditions (Higgins 2011). a measure of the amount of pain relief on a 1 to 10 scale) or as dichotomous data (i.e. Nonhormonal medications (tranexamic acid or NSAIDs) and other hormonal therapies (luteal phase progestins or combined oral contraceptives) are considered secondary options with similar effectiveness.3 Desire for contraception, presence of dysmenorrhea, and comorbidities should be considered when discussing treatment options with individual patients. We included nine additional studies (, S19 OR S20 or S21 or S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31, TX ( (singl* n1 blind*) or (singl* n1 mask*) ) or TX ( (doubl* n1 blind*) or (doubl* n1 mask*) ) or TX ( (tripl* n1 blind*) or (tripl* n1 mask*) ) or TX ( (trebl* n1 blind*) or (trebl* n1 mask*) ), TX ( (trebl* n1 blind*) or (trebl* n1 mask*) ), S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16, TX mesalamine or naproxen or niflumic acid or oxyphenbutazone or pentosan sulfuric polyester or phenylbutazone or piroxicam or prenazone or salicylates or sodium salicylate or sulfasalazine or sulindac or suprofen or tolmetin, TX ibuprofen or indomethacin or ketoprofen or ketorolac or ketorolac tromethamine or meclofenamic acid or mefenamic acid, TX diflunisal or dipyrone or epirizole or etodolac or fenoprofen or flurbiprofen or glycyrrhizic acid, TX ampyrone or antipyrine or apazone or aspirin or bufexamac or clofazimine or clonixin or curcumin or dapsone or diclofenac, (MH "Antiinflammatory Agents, NonSteroidal+"), 3.1 Celecoxib (COX2specific): vs placebo TOPAR difference, 3.2 Etoricoxib (COX2specific): vs placebo TOPAR difference (timeweighted scale), 3.3 Naproxen vs placebo TOPAR difference (timeweighted scale), 5.1 Indomethacin vs placebo (0 to 18 scale), 9.3 Celecoxib (COX2specific): vs placebo, 9.7 Etoricoxib (COX2specific): vs placebo, 12.2 Celecoxib (COX2specific): vs placebo, 2.1 Ibuprofen vs etoricoxib TOPAR 6 difference (timeweighted scale), 3.1 Naproxen vs etoricoxib (COX2specific): TOPAR8, 3.2 Naproxen vs celecoxib (COX2specific): TOPAR8, Inclusion: regularly occurring menstrual pain requiring medication, Differences in baseline pain levels were reported therefore calculations of outcomes were transformed to difference from base value. Pini P, These studies analysed data for 272 women, 187 in crossover studies and 85 in parallelgroup studies. This resulted in an odds ratio for pain relief (all NSAIDs versus placebo) of 5.73 (95% CI 4.45 to 7.38, 19 studies, I2 = 18%). Sikstrom B, Zhu X, When I first got Mefenamic Acid it helped but over 3 months it actually made things worse too. Vecchio TJ, We planned sensitivity analyses for the primary review outcomes to determine whether the results were robust to decisions made during the review process. 29 latin square.ti,ab,hw,tn,mf. Pulkkinen MO. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding. (303) We considered the following methods of allocation concealment adequate: We deemed the risk of bias low if one of these methods was described. This method of analysis permits the use of more of the available data but is likely to widen confidence intervals, with the possible consequence of disguising clinically important heterogeneity (differences between the studies). This can most easily be achieved by metaanalysis. 12 or/711 (6251) We checked the abstracts of major scientific meetings and the reference lists of relevant articles. 14 women randomised and analysed, Piroxicam betacyclodextrin 20 mg versus naproxen sodium 550 mg, Inclusion: women with severe primary dysmenorrhoea, physical and pelvic exam, Naproxen (250 mg as needed, max. Moreover the funnel plot suggested a mild trend towards publication bias, with smaller negative studies less likely to be included in the review. They analysed data for 805 women, 458 in crossover studies and 347 in parallelgroup studies. Comparison 2 Aspirin vs NSAIDs, Outcome 3 Gastrointestinal adverse effects. 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